We're a biophysics lab. We investigate biological spatial organization on the mesoscale (10 nm - 10 microns) and the role of mechanical cues in cellular decision-making. Current research directions include the mechanobiology of tumor progression, the organization of the DNA inside the nucleus, and single-molecule measurements of transport through biological pores and channels.
We also invent and refine tools for precision control and characterization of cells and tissues. Control technologies include light-powered proton pumps, which allow us to optically manipulate the proton-motive-force (pmf) within living cells. Characterization technologies include super-resolution light microscopy. Our lab is located in the Shriram Center at Stanford University.
Beyond classical biophysics, we are also curious about how scientists can identify the most important and meaningful unsolved scientific and medical problems. Since there are more than 24 million publications in PubMed, the conventional tools for staying abreast of new advances would appear to be insufficient.
We have begun to use machine-learning and statistical approaches to guide us towards the most meaningful open questions. We think there is a central role of the patient in biomedical research; without knowing what patients actually want and need, it's hard for scientists to make the best choices about their research directions.
Major Research Directions: Patterns, Energy, and Information
Single molecule studies of the Nuclear Pore Complex
In collaboration with Karsten Weis, we are using single-molecule tracking approaches to learn how the NPC controls access to the nucleus. The image shows a schematic of a NPC in the nuclear membrane, and a single cargo transiting the pore. The panel below shows a single cargo being tracked as it translocates the pore. The NPC is both highly selective and efficient; our goal is to understand how the pore implements those apparently conflicting goals. Moreover, we would like to clarify the fundamental basis for the pore's ability to efficiently rectify molecular transport.
Genome-wide coordination of gene expression
Imagine you are an orchestra conductor directing a symphony. If you're good at what you do, everything will sound right. How does the genome solve the equivalent problem, except without a conductor? We use genome-edited cell lines to investigate how DNA-looping and chromatin compaction influence transcriptional regulation. The image above shows a single nucleus. The DNA is blue, single RNA transcripts are red/yellow.
Mechanobiology of multicellular structures
How do multicellular structures interact with biological matrices such as collagen? We use mammary acini as our basic model system. Mammary acini are composed of about 100 cells and are the basic functional and anatomical units of the human breast. We use mammary acini to explore how collections of cells generate mechanical cues and how these cues spread through biological gels, influencing the decisions of other cells and multicellular structures. The image above shows several hundred mammary acini (tiny red dots) deposited on a collagen matrix (green).